Is ATAD3A p.Ala74Ser (c.220G>T) pathogenic?

ATAD3A p.Ala74Ser (c.220G>T) is classified Uncertain significance in ATAD3A (ClinVar, Single submitter, 1 submitter; last evaluated 2017-11-29). AlphaMissense: likely benign (0.321); Very rare (popmax 0.00153%, nfe); Associated with Inborn genetic diseases.

What condition is associated with ATAD3A p.Ala74Ser (c.220G>T)?

ATAD3A p.Ala74Ser (c.220G>T) is associated with Inborn genetic diseases (ClinVar).

How common is ATAD3A p.Ala74Ser (c.220G>T) in the general population?

ATAD3A p.Ala74Ser (c.220G>T) is very rare (popmax 0.00153%, nfe) (gnomAD).

What do computational predictors say about ATAD3A p.Ala74Ser (c.220G>T)?

AlphaMissense predicts likely benign (score 0.321) — an in-silico prediction, not a clinical call.

ATAD3A p.Ala74Ser

c.220G>T · rs141392786 · VCV985480

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.321 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00153%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.321	likely benign
REVEL	0.641	indeterminate
SaProt	LLR -11.68	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.4, phastCons 1
Regional constraint	o/e 0.73	unconstrained · MANE · 5,138 bp · p 0.00048 · regional, not allelic
Overall
CADD	24.1	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00153% European (non-Finnish) · 18/1,179,958 alleles

Filtering AF 0.000953% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000787%

Overall 0.00112% 18/1,613,910 alleles · very rare

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: ATAD3A
Protein: p.Ala74Ser
Coding: c.220G>T
MANE Select: NM_001170535
dbSNP: rs141392786
Type: single nucleotide variant
Location: chr1:1516026 (GRCh38)
Gene constraint: LOEUF 0.861 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.35

Full ATAD3A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ATAD3A p.Ala74Thr Uncertain significance ★ ⚠ same residue
ATAD3A p.Ala62Val Uncertain significance ★★ ⚠ same condition
ATAD3A p.Arg138Trp Uncertain significance ★★ same condition
ATAD3A p.Arg188Gln Uncertain significance ★★ ⚠ same condition
ATAD3A p.Arg208Cys Uncertain significance ★★ same condition
ATAD3A p.Arg212Cys Uncertain significance ★★ ⚠ same condition
ATAD3A p.Arg273Cys Uncertain significance ★★ ⚠ same condition
ATAD3A p.Arg327Gln Uncertain significance ★★ ⚠ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/atad3a-p-ala74ser (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown